Organization for Validation

To describe the functions and responsibilities of the validation team to meet the cGMP compliance 

It is the responsibility of all concerned departments to follow the procedure. The QA manager is responsible for SOP compliance. 

All validation activities through the different progress steps should be coordinated by one person, preferably the quality assurance manager. 

The team should consist of managers of the departments involved in the validation and outside vendors (if applicable) for example  

The executive part of the validation work should be delegated to dedicated personnel  

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Method validation guidelines for use in trace analysis have been proposed by various authors, but there is little consistency in the recommended approaches. The general validation guidelines proposed by standards organizations such as ISO (International Organization for Standardization), DIN (Deutsches Institut fUr Normung German Institute for Standardization) and others are often not well defined and consequently... 

Once soil samples have been analyzed and it is certain that the corresponding results reflect the proper depths and time intervals, the selection of a method to calculate dissipation times may begin. Many equations and approaches have been used to help describe dissipation kinetics of organic compounds in soil. Selection of the equation or model is important, but it is equally important to be sure that the selected model is appropriate for the dataset that is being described. To determine if the selected model properly described the data, it is necessary to examine the statistical assumptions for valid regression analysis. 

Science cannot be performed without an accurate system of measurement, which is globally standardized and compulsory. Units and standards of measurement are agreed upon and harmonized on an international basis by the Bureau International des Poids et Mesures in Sevres, France, and by the International Organization for Standardization in Geneva, Switzerland. The units and standards are then laid down in national laws. Nearly all countries have accepted the Systeme International d Unites (SI units) as their system of measurement. This also applies to countries that had been accustomed to use British units like Australia, Canada, South Africa and the United States. In Britain, SI units are official from January 2010. The valid standards are available from the competent bureaus, for example Bureau International des Poids et Mesures, www.bip.fr National Measurement Institute (Australia), www.measurement.gov.au National Institute of Standards and Technology (NIST, USA), www.physics.nist.gov/ Pubs/SP811/... 

The method development process with the multisorbent plate consists of three steps. In step 1, the sorbent chemistry and the pH for loading, washing, and elution are optimized. In step 2, optimization of the percentage organic for wash and elution and the pH of the buffer needed is carried out. Step 3 is validation the method developed from the results of the previous two steps is tested for linearity, limits of detection, quantitation of recovery, and matrix effects using a stable isotope-labeled analyte as an IS. 

The United Nations Globally Harmonized System of Classification and Labelling of Chemicals (GHS) includes an internationally standardized guidance procedure on Transformation/Dissolution Protocol (T/DP) for metals and sparingly soluble metal compounds (United Nations, 2007), recently validated by the OECD (Organization for Economic Cooperation and Development). To establish the acute aquatic hazard classification level of a metal-bearing substance under the GHS, data from the T/DP are compared with an acute ecotoxicity reference value (ERV) derived under conditions similar to those of the T/DP. 

For validation the following robustness factors should be considered different lots of the capillary, temperature ( 2°C), applied voltage/current ( 2% relative), buffer electrolyte concentration ( + 10% relative), pH ( 0.1), concentration of additives, e.g., organic modifiers or chiral additives ( 10% relative), injection time ( 0.5s), detection wavelength ( + 2nm), batch-to-batch variation of chiral selectors ( 2—3 different lots), CE instruments (two instruments of two different manufacturers preferentially). 

Sorption. Kqp values have been looked upon as constant for neutral organic chemicals. Independent of soil type (73). The parameter Is valid for comparison of leaching potential of pesticides with widely varying water solubility however. It Is difficult to make quantitative comparisons among polar organics. For example, note the wide range In Kq, for oxamyl described In Table IV. This may be due In part to Interactions with soil mineral fractions which become Important when the soil organic matter content Is low (56,112). Also, use of water solubility... 

During the last 10 years it has been attempted to develop in vitro methods as alternative methods in the study of effects where animal models have previously been necessary. Such effects include skin and eye irritation and specific organ damage. Validation programs have been launched, and some of the above-mentioned methods have been sufficiently validated for use in regulatory risk assessment of chemical substances and may now for certain purposes be used as stand-alone evidence. Results from nonvahdated methods can in some cases be used as supportive evidence to human and animal data. 

From the results of the viable count, calculate the volume of each organism that contains between 10 and 100 CPUs and use this for validation, growth promotion, and stasis testing. A concurrent viable count... 

Within an organization, a validation master plan can be developed for ... 

The ideal validated method would be the one that has progressed fully through a collaborative study in accordance with international protocols for the design, conduct, and interpretation of method performance studies. A typical study of a determinative method conducted in accordance with the internationally harmonized International Organization for Standardization (ISO)/International Union for Pure and Applied Chemistry (IUPAC)/AOAC International (AOAC) protocol would require a minimum of up to five test materials including blind replicates or split-level samples to assess within-laboratory repeatability parameters, and eight participating laboratories (15). Included with the intended use should be recommended performance criteria for accuracy, precision and recovery. 

World Health Organization, in Validation of Analytical Methods for Food Control, Joint FAO/IAEA Expert Consultation 2-4 December 1997, Vienna, Austria, Food and Agriculture Organization of the United Nations. FAf) Food and Nutrition Paper No 68, Rome (1998). 

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