Validation, method summary

The method for sterility testing of (product name) USP is manufacturing site SOP and the microbiological sterility method validation summary report is provided in (provide reference attachment number). The USP bacteriostasis/fungistasis test was performed to validate the sterility test method... 

Sterility testing of (specify name) USP microbiological sterility method validation summary report... 

A summary page is generated upon completion of the tablet method validation. This gives the user a quick reference of where to find the data, and the conclusions of each experiment. It also alerts the analyst to any potential degradation. An example of a method validation summary for drug product can be found in Table 2. 

Analytical method validation summaries/reports—qualification of methods for GLP toxicology studies... 

Once the determinative or confirmatory method has been developed to take full advantage of the chemical properties of the analyte molecule, a study is necessary to prove that the method is valid. Criteria for method validation are outlined in guidelines from the US FDA, US EPA, and EU. A summary of the differences in regulatory requirements for method validation is provided in Table 3. The parameters addressed by all of the regulatory guidelines include accuracy, precision, sensitivity, specificity, and practicability. 

DeVita and Crunkilton (1998) have examined QC associated with the use of SPMDs. The results of their study demonstrated that quality control measures applied to SPMD analysis met or surpassed conventional guidelines (EPA Method 610 for PAHs in water was used for this comparison) for precision and accuracy. This elevated level of data quality was achieved even though measurements of both overall precision and accuracy of SPMD data encompassed more steps (each with the potential for variability) than the conventional method. In summary, DeVita and Crunkilton (1998) found that QC measures could be used to validate data from the analysis of SPMDs used in the field. In view of the state of SPMD QC, it appears that the SPMD approach for monitoring hydrophobic organic contaminants is equivalent to some EPA-approved methods. 

Summary of the role of a ruggedness test in a method validation program... 

A summary of the results of the method validations appears in Table VI. 

Table VI. Summary of Results for Method Validations HCCP HCBD 1,2-DCP...

A detailed method validation report may not be necessary until submission of the final market application. However, summary reports should be available to facilitate efficient data retrieval and fulfill requests from regulatory agencies for the information when required. 

It is very useful to summarize all method validation data into a tabular format. The tabulated summary will give a quick overview of the validation data. Often, the analyst may be so involved during the actual validation work that some errors escaped detection. Table 2.7 is an example of how data can be recorded. 

Summary of process and method validations and revalidations, when applicable. 

In this guidance the FDA offers some direction for the demonstration of comparability. They request that the manufacturer provide evidence that the methods, facilities, and controls that were used to manufacture previous products conformed to cGMPs and to other applicable regulatory requirements. In addition they request the submission of validation summaries, as well as product characteristics such as total nucleated cell count, viable CD34 cell count, and number of colony-forming units. Stability data and information from the scientific literature can also be used. Clinical outcomes can be part of the comparability demonstration. 

Data Elements Use this section to provide thorough and complete documentation of the validation of the analytical method. Include summaries of experimental data and calculations substantiating each of the applicable analytical performance parameters. These parameters are described in the following section. 

TABLE 1 Summary of TLC Method Validation for Drug Substance ... 

We have applied this protocol to the evaluation of the measurement uncertainty for a method for the determination of three markers (Cl solvent red 24, Cl solvent yellow 124 and quinizarin (1,4-dihydroxyanthra-quinone)) in road fuel. The method requires the extraction of the markers from the sample matrix by solid phase extraction, followed by quantification by HPLC with diode array detection. The uncertainty evaluation involved four experimental studies which were also required as part of the method validation. The studies were precision, trueness (evaluated via the analysis of spiked samples) and ruggedness tests of the extraction and HPLC stages. The experiments and uncertainty calculations are described in detail in Part 2. A summary of the uncertainty budget for the method is presented in Fig. 3. 

The emphasis in the IND for phase 1 studies is on the identification and control of the new drug substance. As clinical development progresses, additional information should be submitted for new processes and larger-scale manufacturing procedures used to produce materials for the phase 2 and phase 3 clinical trials. Information for phase 1 studies may be submitted in a summary report with brief descriptions. The summaries are expanded and data are added as development and clinical trials progress. For example, established specifications and method validation need not be submitted for phase 1, but a detailed listing of all tests with a complete description of the corresponding procedures with validation information is expected by phase 3. 

Method transfer for ore-Studv validation Method development summary report Data table showing acceptable method performance Method is ready for pre-study validation... 

Analysis 5. Compute performance statistics Use appropriate statistical methods to compute these values. For example, EXCEL program for computation of accuracy/precision summary statistics for prestudy methods validation (http //www. aapspharmaceutica.com/ inside/sections/biotec/ applications/lba.asp)... 

In summary, these results demonstrate that for CSIA, in addition to the method validation required for quantitative determinations, the methods... 

Miller K J, Bowsher R R, Celniker A, et al. (2001). Workshop on Bioanalytical Methods Validation for Macromolecules Summary Report. Pharm. Res. 18 1373-1383. 

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