Validation, method protocol

BERM-5 presented the changing outlook of the AOAC International in recognizing the usefulness of incorporating RMs for use in conjunction with their methods validation protocol. 

Different sample materials often need some adjustment of pesticide residue methods. The insufficient consideration of matrices in thcNKML method validation protocol may be a tribute to the wide scope of this standard. 

DQ is performed by the supplier of the equipment or system at the supplier s factory as part of the factory acceptance test (FAT). IQ (based on site acceptance test—SAT), OQ, and PQ are performed on-site at the GMP facility. For a GMP manufacturing facility, the validation activities include the facility design, FTVAC system, environment control, laboratory and production equipment, water system, gases and utilities, cleaning, and analytical methods. Validation protocols (IQ, QQ, and PQ) are prepared for each item, listing all critical steps and acceptance criteria. Deviations are reviewed and resolved before the validation activity proceeds to the next phase. 

The method validation experiments should be well planned and laid out to ensure efficient use of time and resources during execution of the method validation. The best way to ensure a well-planned validation study is to write a method validation protocol that will be reviewed and signed by the appropriate person (e.g., laboratory management and quality assurance). 

Execution of the method validation protocol should be carefully planned to optimize the resources and time required to complete the full validation study. For example, in the validation of an assay method, linearity and accuracy may be validated at the same time as both experiments can use the same standard solutions. A normal validation protocol should contain the following contents at a minimum ... 

Similar to the methods validation protocol, it is recommended to obtain approval signatures from both the director of quality control and quality assurance because of the regulatory criticality of a method transfer exercise. 

TABLE 9-5. Range for Recovery Experiment for CU and Assay Method to Be Defined in Method Validation Protocol... 

Abstract Although the validation process necessary to ensure that an analytical method is fit for purpose is universal, the emphasis placed on different aspects of that process will vary according to the end use for which the analytical procedure is designed. It therefore becomes difficult to produce a standard method validation protocol which will be totally applicable to all analytical methods. It is probable that far more than 30% of the methods... 

DeSain, C. Master method validation protocols. BioPharm 6 30-34, 1992. 

When samples contain very low levels of degradation products, recovery studies are performed by spiking actual samples with known degradation products at levels consistent with the specification. Acceptance criteria for % recovery and precision should be consistent with the requirements established in the original method validation protocol. Un-spiked samples should also be run to enable correction for any amount present in the actual sample. 

The validation documentation typically consists of a protocol, analytical data, and a final report. One approach to simplifying validation documentation is to focus on a thorough protocol with preapproved acceptance criteria, which are necessary to determine whether the validation results demonstrate that the method is fit for purpose. In early development, this protocol may be captured in a lab notebook which could be in either a paper or an electronic environment. There is an ever increasing trend in the use of electronic laboratory notebooks which makes it simple to execute previously developed protocols. Later in development, the protocol should be a unique document, which may have data tables to enter the test results, requiring only a short executive summary to summarize the results and a reference or attachment of raw data. A development lab will often use these well-developed and optimized master method validation protocols" " as templates for subsequent validations. A copy of the method procedure and, where available, a method development report may be appended to the validation protocol. In general, the validation protocol should contain the following ... 

At the conclusion of development, when methods are locked, it is becoming more common for the analysts to ask the quality unit for input and comment on the proposed method package before final validation. Such a method test drive can avoid problems with the formal transfer taking place later. This process has been termed an analytical method evaluation ring test (AMERT) by Crowther and associates and was presented and described elsewhere. In brief, this process allows the quality unit to make comments and suggestions to their R D colleagues before the final validation of the method. It is also becoming more common for the quality unit to approve method validation protocols. This provides the quality unit with an opportunity to ensure that the method meets the performance expectations to enable routine use in the quality environment. In some cases, covalidation by the R D and Quality Units (discussed below) replaces formal method transfer. Thus, the frequently seen throw the method over the fence syndrome is avoided. 

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