Quality assurance validation

Several key issues have to be addressed in the downstream processing of biopharmaceuticals regardless of the expression system. The removal of host cell proteins and nucleic acids, as well as other product- or process-related or adventitious contaminants, is laid down in the regulations and will not differ between the individual expression hosts. The identity, activity and stability of the end product has to be demonstrated regardless of the production system. The need for pharmaceutical quality assurance, validation of processes, analytical methods and cleaning procedures are essentially the same. 

The validation master plan is a summary document stating the intention and the methods to be used to establish the adequacy of the performance of the equipment, systems, controls, or process to be validated. It is approved by the quality assurance, validation, production, and engineering groups. 

Reports and notes on experiences with quality assurance, validation and accreditation... 

This Handbook aims to explain terminology widely used, and sometimes misused, in analytical chemistry. It provides much more information than the definition of each term but it does not explain how to make measurements. Additionally, it does not attempt to provide comprehensive coverage of all terms concerned with chemistry, instrumentation or analytical science. The authors have addressed primarily those terms associated with the quality assurance, validation and reliability of analytical measurements. The Handbook attempts to place each term in context and put over concepts in a way which is useful to analysts in the laboratory, to students and their teachers, and to authors of scientific papers or books. This approach is particularly important because official definitions produced by many international committees and organisations responsible for developing standards are frequently confusing. In a few cases the wording of these definitions completely obscures their meaning from anyone not already familiar with the terms. 

The variety of complex terms used in the Quality Assurance aspect of analytical measurement can be the cause of considerable confusion.This unique handbook explains the most widely-used terminology in language that is readily understood, and attempts to place each term in context. Concepts are described in a way that is useful to all practitioners, particularly those concerned with quality assurance, validation and reliability of analytical measurements. Explanations of terms are always in line with the "official definition", often developed by international committees. 

Key words Clinical spectrophotometry Quality assurance Validation Reference materials Spectrophotometric... 

Keywords Accuracy Analytical procedure Measurement assurance Measurement uncertainty Quality assurance Validation... 

Head of validation Head of quality assurance Validation representatives Validation representative ... 

Medical technologists perform highly complex laboratory tests under the supervision of a medical director. They may specialize in various components of laboratory work, such as quality assurance, validation, or training, or they may specialize in a particular field, such as histotechnology or cytotechnology. 

In Figure 7.53 a flow-injection interface for fluorometric monitoring of focused microwave-assisted Soxhlet extraction is represented [195]. This assembly allows real-time online monitoring of the PAHs extracted from solid samples in each Soxhlet cycle and provides qualitative and semi-quantitative information from natural and spiked samples. The method has been applied to a certified reference material (CRM 524, BCR, industrial soil/organics) for quality assurance/validation. The proposed technique is as efficient as conventional Soxhlet to extract PAHs from soils but with a drastic reduction of both extraction time and organic solvent disposal. 

All formulas are to be written out by hand with the specific numbers in the right places on a sheet provided for the purpose, and the calculations are to be done by calculator. Caution Write the numbers exactly as printed, do not round any digits, or the quality assurance unit (a sort of corporate vice squad) will not approve the report out of fear that someone could have cheated. A validated program can be used. While an Excel spreadsheet as such needs no validation, a simple cell-formula calls for extensive tests and documentation and proof that the sheet is password protected against fraudulent manipulation. On top of that, the analyst s supervisor is required to confirm the calculation and sign off on... 

When testing and analysis are completed, the data can be analyzed and summarized. Statistical methods are often used during this step In a study. Data should first be edited and validated. Quality assurance Information from both the sampling and laboratory analyses should be considered In this validation. Field sampling personnel and laboratory scientists should maintain responsibility for data validation. 

Monitoring programs must have their own quality assurance programs. These may be called project quality assurance plans or protocols for specific purposes O). If reliable vendors of services are used, the bulk of the quality assurance effort can be placed on those activities unique to the program. Without reliable vendors, QA efforts will be ineffective since it is not cost effective to police quality assurance practices at all lower levels nor to screen all data for its validity. 

The program must require the vendors to measure a number of reference samples and/or duplicates submitted in a planned sequence. It should require prompt measurement and reporting of these data and should maintain the results in a control chart format. Prompt feedback and follow-up of any apparent data discrepancies and reconciliation of the results with control charts maintained by the vendors are required to minimize the length of uncertain performance. The quality assurance plan should include random sampling of the vendors data for their validity and conformance with quality assurance requirements. If quality assurance is properly practiced at all levels, an inspection of 5 percent of the total data output should be adequate. 

Obviously, GMP requirements, especially extensive personnel training, calibration, qualification and validation, enhanced documentation, extensive cleaning and sanitation, and sharpened in-process control must considerably influence process organization and output. All these GMP-related activities are costly and time consuming, and will result in decreased productivity and increased production costs. On the other hand, a quality assurance system contributes to consistent production with a lower number of rejected batches and complaints. 

Zeisler R, Wise SA (1985) Quality assurance and protocols in sampling and sample preparation of biological samples. In Wolf WR, ed. Biological Reference Materials Availability, Uses and Need for Validation of Nutrient Measurement, pp. 257-279. John Wiley and Sons, New York. 

Byrne AR, and Kucera J (1997) Role of the self-validation principle of NAA in the quality assurance of bioenvironmental studies and in the certification of reference materials. Proc. Int. Symp. Harmonization of Health Related Environmental Measurements Using Nuclear and Isotopic Techniques, Hyderabad, India, pp 223-238. IAEA Vienna. 

Apart from innovative work, RMs are essential during exerdses such as the introduction to a laboratory of a method from elsewhere or the transfer of an established method onto new instrumentation. Even where the conditions for the analysis have been standardized by the manufacturer of a reagent kit, some validation work should still be undertaken so as to have documented data for quality assurance purposes, e.g. accreditation, as a basis for IQC, for later reference when problems which may be related to equipment, reagents or staff etc. need to be investigated. 

The use of reference samples for method calibration and development/validation occurred hand-in-hand with the development of all modern instrumental methods of analysis. In fact, the two developments are intimately linked with one another. As already noted, G-i and W-i (Fairbaim et al. 1951 Stevens i960) illustrate first instance of reference samples specifically developed for calibration purposes. Following that, the use of BCR-i as a reference sample throughout the lunar program (Science 1970) is a prime illustration of the quality assurance and method validation applications in large-scale inter-laboratory measurement programs. 

The software life cycle activities extend until retirement of the software. However, in a manner of speaking, life cycle activities extend even beyond retirement since the data must be able to be reconstructed at any time during the life of the product, i.e., the archived record must always be accessible and readable even if the software is no longer commercially available or typically employed in the laboratory. Additional software validation includes implementation of the code and integration and performance testing. There also must be system security, change control procedures, audit trails, calibration, preventative maintenance, and quality assurance. 

Validation of extraction procedures is frequently lacking. A good assessment of quality assurance implies that the extraction recoveries are verified, e.g. by spiking of standard addition. A major drawback is that the spike is not always bound the same way as the compounds of interest. For the development of good extraction methods, materials with an incurred analyte (i.e. bound to the matrix in the same way as the unknown), which is preferably labelled (radioactive labelling would allow verification of the recovery), would be necessary. Such materials not being available, the extraction method used should be validated by other independent methods, e.g. by verification against known samples and by use of a recovery SPC chart. A mere comparison of extraction methods is no validation. 

In the field of RM certification, NAA represents a major analytical technique. It possesses unique quality assurance and self-verification aspects. Not surprisingly, therefore, NAA has been used to certify NIST standard reference materials [470]. By analogy, NAA has also been instrumental in analysing the EC polymer reference materials within the framework of the PERM project [1]. NAA was also used to validate a TXRF procedure for the determination of additives containing Ti, Zn, Br, Cd, Sn, Sb and Pb [56],... 

Independent quality assurance assessment of validation effort... 

In analytical practice, they are best recognized by the determination of xtest as a function of the true value xtrue, and thus, by analysis of certified reference materials (CRMs). If such standards are not available the use of an independent analytical method or a balancing study may provide information on systematic errors (Doerffel et al. [1994] Kaiser [1971]). In simple cases, it may be possible, to estimate the parameters a, / , and y, in Eq. (4.5) by eliminating the unknown true value through appropriate variation of the weight of the test portions or standard additions to the test sample. But in the framework of quality assurance, the use of reference materials is indispensable for validation of analytical methods. 

Wegscheider W (1996) Validation of analytical methods. In H. Gunzler (ed) Accreditation and quality assurance in analytical chemistry. Springer, Berlin Heidelberg New York... 

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