Method validation analytical

The specification development process is a data-driven activity that requires a validated analytical method. The levels of data needed include assay precision, replicate process results (process precision), and real-time stability profiles. A statistical analysis of these data is critical in setting a realistic specification. Most often, aggregation and fragmentation degradation mechanisms are common to protein and peptide therapeutics. Therefore, the SE-HPLC method provides a critical quality parameter that would need to be controlled by a specification limit. 

Reliable residue data are generated during the development of an a.i. to support the assessment of the consumer risk (residue data and toxicological data) and the impact on the environment (fate and behavior, efficacy and ecotoxicological data). It is critical that these analytical methods are reliably validated. In the guidance document SANCO/3029/99 rev. 4 (11/07/00), harmonized requirements for the residue analytical method are described. Validated analytical methods are required for the following studies ... 

Wille K, Vanden Bussche J, Noppe H, De Wulf E, Van Caeter P, Janssen CR, De Brabander HF, Vanhaecke L (2010) A validated analytical method for the determination of perfluorinated compounds in surface-, sea- and sewagewater using liquid chromatography coupled to time-of-flight mass spectrometry. J Chromatogr A 1217(43) 6616-6622... 

Burgess, C., Valid Analytical Methods and Procedures, ISBN 0-85404-482-5, The Royal Society of Chemistry, Cambridge, UK, 2000. 

Consideration of the above requirements confirms that in future all methods must be fully validated if at all possible, i.e. have been subjected to a collaborative trial conforming to an internationally recognised protocol. In addition this, as described above, is now a legislative requirement in the food sector of the European Union. The concept of the valid analytical method in the food sector, and its requirements, is described below. 

It is also possible for a perfectly valid analytical method to become less valid when used under different conditions. For example, the poten-tiometric measurement of pH is temperature-dependent and the use of reference and test solutions at different temperatures without any compensation will result in values being consistently higher or lower than they should be. 

Toxicokinetics has become a critically important component of any nonclinical program (see discussion in Section 14.10). Current ICH guidelines require the determination of animal pharmacokinetics at all dose levels administered on at least 2 days (beginning and end) during a nonclinical toxicology study.5 Similarly, this requires the development of a validated analytical method for the determination of parent drug (and possible major metabolites). 

QC tests are carried out according to validated analytical methods or established methods from pharmacopoeias US Pharmacopoeia and British Pharmacopoeia. Exhibit 10.2 lists some of the QC analytical methods performed on drug intermediates and products. 

Putting in time and effort up front wiU help any environmental analysts to find a way throngh the method validation maze and eliminate many of the problems common to inadeqnately validated analytical methods. 

Reliable quality control in the field of pharmaceutical analysis is based on the use of valid analytical methods. For this reason, any analytical procedures proposed for a particular active pharmaceutical ingredient and its corresponding dosage forms shonld be validated to demonstrate that they are scientifically sonnd nnder the experimental conditions intended to be used. Since dissolntion data reflect drng prod-net stability and quality, the HPLC method used in snch tests shonld be validated in terms of accuracy, precision, sensitivity, specificity, rngged-ness, and robustness as per ICH guidelines. 

Aspects which are generally relevant to validate analytical methods Precision... 

Testing the final product, using validated analytical methods, in order to meet specihcations... 

The validation parameters that will be evaluated will depend on the type of method to be validated. Analytical methods that are commonly validated can be classified into three main categories identification, testing for impurities, and assay. Table 3 lists the ICH recommendations for each of these methods. 

Wood, R. (1999), How to validate analytical methods, Trends Anal. Chem., 18, 624-632. 

Design of Facilities Manufacturing Process Validation Analytical Methods Equipment and Computer Systems... 

Burgess, C (2000), Valid analytical methods and procedures a best practice approach to method selection, development and evaluation (Cambridge Royal Society of Chemistry). 

While the provision of suitably validated analytical methods is a necessary requirement for ensuring compliance with MRLs, the method alone is not sufficient to ensure creditable analytical measurements. In addition to selecting suitable methods, the analyst must demonstrate that the method is operating under statistical control in the laboratory and is performed to meet performance specifications as required by the analytical problem. This means that all methods should be applied in an environment with appropriate quality assurance procedures and performance evaluation checks. 

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