Analytical Development and Quality Assurance

Analytical procedures have to be developed for the active ingredient as well as for starting materials and the excipients used in the final formulation. These tests should be able to specify and confirm the identity, purity, potency, stability and consistency of these materials. If significant impurities, degradation products or critical metabolites occur, analytical methods for these will also be required. In-process control methods must be devised and developed to observe all relevant steps of the manufacturing process in order to have adequate control over the inherent variants and to detect potentially harmful contaminants at a stage where they may be easier to trace. 

The spectrum of tests to be employed comprises methods from microbiology, immunology, protein and peptide biochemistry, genetic engineering and physico-chemical methods as well as animal experimentation. If these exist, for example in pharmacopoeias, standard method descriptions have to be followed. 

Critical steps of the manufacturing process and analytical methods have to be validated carefully. Process validation will be required for example for the inactivation or elimination of potentially pathogenic microorganisms (e.g. viruses in cell cultures) from the product. This can be done by running spiked samples through the process or through 

Analytical methods are validated by investigating the specificity, sensitivity, detection limits, quantification limits, accuracy (of the individual result), precision (variation between different tests), applicability and practicability under laboratory conditions and the robustness (susceptibility to interference) of the method. This enables the organization itself to employ these tests much more consciously and with better results, but it also serves the purpose of enabling the registration authorities to use these tests for the regular batch control tests. Official guidelines by the regulatory authorities for the validation of analytical methods and processes are available for consultation. 

Good Manufacturing Practice (GMP) standards are a further step towards the concept of total quality . Implementing and maintaining a GMP status requires commitment of the entire organization and constant attention by those who are in charge of quality assurance. Because of the complexity and wide scope of the subject and the amount of paperwork (some translate GMP as Give Me Paper ) extra personnel or external consultants will most likely be required. 

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The analysis of some brominated flame retardants, such as TBBPA, HBCDs and the higher brominated PBDEs, is a relatively new challenge for most analytical laboratories. Special emphasis must be given to the need of an adequate Quality Assurance/Quality Control (QA/QC) protocol, which is necessary for the reliable analysis of these environmental contaminants at trace levels (Papke et al. 2004). Literature on the analysis of brominated flame retardants in different matrices, paying special attention to new analytical developments and quality assurance requirements, has recently been reviewed by Covaci et al. (2007). In addition, a recent paper of Kierkegaard et al. (2009) discusses the problems and challenges of the environmental analysis of the higher brominated compounds. 

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