Validation bioanalytical

Partial validation modification of validated bioanalytical methods that do not necessarily call for full revalidation. 

Partial Validation. Partial validations are modifications of already validated bioanalytical methods. Partial validation can range from as little as one intraassay accuracy and precision determination to a nearly full validation. Typical bioanalytical method changes that fall into this category include but are not limited to ... 

Cross-Validation. Cross-validation is a comparison of validation parameters when two or more bioanalytical methods are used to generate data within the same study or across different studies. An example of cross-validation would be a situation where an original validated bioanalytical method serves as the reference and the revised bioanalytical method is the comparator. The comparisons should be done both ways. When sample analyses within a single study are conducted at more than one site or more than one laboratory, cross-validation with spiked matrix standards and subject samples should be conducted at each site or laboratory... 

Stereoisomer Assays. There are many drugs that are administered as racemic mixtures. They may undergo stereoselective metabolism and/or elimination, and one isomer may be more active than the other. Therefore, there is the need to develop and validate bioanalytical assays for stereoselective determination in bioavailability/bioequivalence studies. All methods used for measurement of stereoisomer should be validated (with emphasis on stereospecificity). For bioequivalence studies of an existing racemic product, a stereospecific assay is not required if the rate and extent of profiles are superimposable (within the usual statistical boundaries) [3,23]. 

Bio analytical Methodology Bioanalytical methods for BA and BE studies should be accurate, precise, selective, sensitive, and reproducible. A separate FDA guidance entitled Bioanalytical Method Validation (May 2001) is available to assist sponsors in validating bioanalytical methods. 

Develop and validate bioanalytical method for drug candidate and known metabolites in human physiologic fluid specimens. 

Antibodies analyzed (using a validated bioanalytical chemistry method to be transferred to the service provider) for test article concentration to assess extent of exposure Blood specimens collected prior to the first, seventh, and fourteenth dose to be analyzed (using a developed assay to be transferred to the service provider) for antibodies to the test article... 

Cross-validation is conducted when two validated bioanalytical methods are used within the same study or submission, for example, ELISA assay to Biacore and ELISA to a liquid chromatography/mass spectrometry. It is recommended that test samples (spiked and/or pooled incurred samples) be used to cross-validate the bioanalytical methods. Data should be evaluated using an appropriate predefined acceptance criteria or statistical method [12,13]. It should be cautioned that many times the methods that are being cross-validated may not have the same range of quantification. In these situations, it is necessary to prepare spiked samples within the range that are common to both methods for comparison. 

Validated bioanalytical assays are essential and have to be developed to characterize the biopharmaceuticals during the production process (e.g. in-process control) and to release the final product for use as a drug in humans. These assays are applied to determine characteristics such as purity/impurities, identity, quantity, stability, specificity, and potency of the recombinant protein during drug development. Since the very diverse functions of different proteins heavily depend on their... 

On the other hand, bioanalytical assays are necessary to determine and quantify the protein drug in biological fluids. For example, validated bioanalytical assays are the key in the quantitation of the protein drug in the course of pharmacokinetic studies (see Chapter 8). Especially in the case of humanized/human monoclonal antibodies, bioanalytical assay development in human serum/plasma is challenging because the therapeutic concentration of antibodies can be very low (0.1 to 10 xg mL or even lower), and because these antibodies are so similar to the native human antibodies that circulate in the blood in very high concentrations of 10000 xg mL k... 

Another maj or topic of scientific and regulatory consideration in the development of therapeutic proteins is the assessment of undesired immune responses to the drug that may lead to a reduction in efficacy and to adverse reactions. This assessment also requires validated bioanalytical assays. 

Selection of metabolites for monitoring by a validated bioanalytical method in selected nonclinical toxicology studies and clinical studies (Baillie et al., 2002 Humphreys and Unger, 2006) ... 

Validation is the process and documentation of the specific laboratory investigations that demonstrate an analytical method is suitable and reliable for its intended appUcations [31]. A validated bioanalytical method must demonstrate accuracy, precision, selectivity, sensitivity, reproducibility, and stability in order to support GLP toxicology studies and clinical trials. Below are the principles and acceptance criteria in each area. 

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