External quality control

Regulatory QSAR models are more demanding because of their relationship with the law, which introduces requirements, some internal to the QSAR model process, others external. Internally the model needs a high level of quality control. Externally, the model has to comply with, and be suited for, the regulatory use. 

In HPLC, a sample is separated into its components based on the interaction and partitioning of the different components of the sample between the liquid mobile phase and the stationary phase. In reversed phase HPLC, water is the primary solvent and a variety of organic solvents and modifiers are employed to change the selectivity of the separation. For ionizable components pH can play an important role in the separation. In addition, column temperature can effect the separation of some compounds. Quantitation of the interested components is achieved via comparison with an internal or external reference standard. Other standardization methods (normalization or 100% standardization) are of less importance in pharmaceutical quality control. External standards are analyzed on separate chromatograms from that of the sample while internal standards are added to the sample and thus appear on the same chromatogram. 

In addition to fulfilling the in-house requirements for quality control, state and local air monitoring networks which are collecting data for compliance purposes are required to have an external performance audit on an annual basis. Under this program, an independent organization supplies externally calibrated sources of air pollutant gases to be measured by the instrumentation undergoing audit. An audit report summarizes the performance of the instruments. If necessary, further action must be taken to eliminate any major discrepancies between the internal and external calibration results. 

Support for sites is multi-tiered and includes participation by numerous federal, state, private, academic, and tribal organizations. Network operation includes rigorous field and laboratory quality assurance/quality control (QA/QC), including an external quality assurance program and periodic external on-site audits. 

It must be remarked that terminology is not consistent and there are many widely used synon)ms. Quality control in this Chapter refers to practices best described as internal quality control. Quahty assessment is often referred to as external quality control, proficiency testing, interlaboratory comparisons, round robins or other terms. Internal Quality Control and External Quality Assessment are preferred because they best describe the objectives for which the RMs are being used, i.e. the immediate and active control of the results being reported from an analytical run or event, and an objective, retrospective assessment of the quality of those results. 

The primary purposes for which reference materials are employed are encompassed within the laboratory Quality Assurance Procedures. Quality assurance comprises a number of management responsibilities which focus on how the laboratory is organized, how it deals with situations, how it interacts with users, together with analytical responsibilities re internal quality control and external quality assessment (Sargent 1995 Burnett 1996). Ideally each component follows a documented protocol and written records of all activities are maintained. 

Tl, Xe and °Y). The US National Institute of Standards and Technology (NIST) operates an external quality control program on a varying schedule from one year to the next (Golas 1998). Details of the current program are available from the NIST website. 

Quality control describes the measures used to ensure the quality of individual results or a batch of results. The measures used will vary according to the particular application. It is a means of evaluating the current performance of the method being used and the general procedures used in the laboratory. There are two types of quality control, namely internal quality control and external quality assessment. These are covered in detail in Chapters 6 and 7, respectively. 

There are two uses of chemical standards in chemical analysis. In the first place, they may be used to verify that an instrument works correctly on a day-to-day basis - this is sometimes called System Suitability checking. This type of test does not usually relate to specific samples and is therefore strictly quality assurance rather than quality control. Secondly, the chemical standards are used to calibrate the response of an instrument. The standard may be measured separately from the samples (external standardization) or as part of the samples (internal standardization). This was dealt with in Section 5.3.2. 

STL s quality-control programme includes the recovery of known additions of analyte, analysis of externally supplied standards, calibration, analysis of duplicates and control charting. Each analyte is monitored by analysing at least one AQC standard for every 20 samples. AQC results are plotted on control charts and action is taken if a point Hes outside +3 standard deviations (SD) or if two consecutive points He outside +2 SDs. 

The cost of appraisal in a laboratory is about measuring the laboratory performance, morritoring of the laboratory processes, doing internal quality control, internal and external laboratory audits and so on. 

Interlaboratory tests are a powerful tool for external quality control (see chapter 15). A laboratory should take part wherever possible. The participation has to be planned. The results and if necessary the corrective actions have to be documented. Procedures have to be accordingly described in the quality manual. 

The introduction of GCP has accelerated the need for quality control and quality assurance, particularly in the field of clinical research. Quality control is carried out by the staff who are responsible for the particular activity, working to SOPs that cover all the tasks under scrutiny. SOPs not only need to be written but must also be updated regularly. Quality assurance is the process which seeks to confirm that SOPs have been observed this is accomplished by the process of auditing. Internal audit departments should be under a separate management from the medical department. Regular audits can not only assure external bodies, such as regulatory authorities, that proper procedures have been followed, but also serve to deter those rare attempts at fraud on the part of clinical investigators, which occasionally become evident. ... 

In order to implement the quality policy in the daily work, quality management systems are installed, covering quality planning, quality control, quality assurance and quality improvement. To ensure that the quality assurance system is in place and effective, external standards are used, for example the DIN EN ISO 9000 ff. standard system, commonly shortened to ISO 9000 (DIN is an acronym for Deutsches InstitutfiXr Normung, meaning German Industry Standard ). 

It is important to issue a common understanding on the topics of method validation, traceability, and uncertainty of measurements. Here, the interrelationships between method validation, traceability, and MU of results will be elucidated. Throughout the landscape of guidelines and standards, the most relevant information is selected, compiled, and summarized. Great importance is attached to the different method performance parameters and their definitions, ways of expression, and approaches for practical assessment. We discuss the role of method validation within QA as well as the topics of standardization, internal and external quality control (IQC and EQC, respectively), and accreditation and the links between these different aspects. 

Within QC, internal and external quality control are distinguished. In general, QA comprises the following topics as also schematized in Figure 6. 

External Quality Control and Accreditation Participation in PT schemes is an objective means of evaluating the reliability of the data produced by a laboratory. Another form of external assessment of the laboratory performance is the physical inspection of the laboratory to ensure that it complies with externally imposed standards. Accreditation of the laboratory indicates that it is applying the required... 

The main external review body in the biopharmaceutical and pharmaceutical industries is the Food and Drug Administration (FDA), but at some later stage it may be necessary to prepare a monograph for the quality control of a new product and this would be achieved by interacting with officials from the United States Pharmacopeia (USP) in order to have a section published in the pharmacopoeia. The purpose of this chapter, therefore, is to introduce both of these organizations and provide an understanding of their basic functions. 

When using medical laboratories, physicians frequently assume that the results provided are accurate and precise. Those working in the laboratory environment know that this is true only within the constraints of the methods, technology and processes available. In this chapter we will explore how internal quality control (IQC) and external quality assurance (EQA) procedures can inform both the analyst and the physician about the limitations of laboratory testing and permit a more intelligent use of laboratory data, while at the same time indicating areas where improvement is required. 

External quality control involves participation in the ERNDIM scheme for quantitative amino acids in plasma. Four pairs of samples with four concentration levels are analyzed throughout the year and their results give an indication of accuracy, precision, linearity, and recovery. 

Quality assessment is performed by including pooled plasma as an internal control in every run. External quality control is achieved using samples obtained from the European Research Network for evaluation and improvement of screening, Diagnosis and treatment of Inherited disorders of Metabolism (ERNDIM) Special Assays Scheme, run according the scheme schedule. 

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