Standard operating procedure validation reports

The requirements or prerequisites of the Basis Documents are fixed. Basis documents have targets they can be updated and are applicable over a longer time interval (e.g. standard operation procedures). Proof Documents contain proofs of operations and the details of the actual stock they are not changeable and are only valid for single incidents (e.g. test reports). 

The VMP should be a summary document and should therefore be brief, concise, and clear. It should not repeat information documented elsewhere but should refer to existing documents such as policy documents, standard operating procedures (SOPs), and validation protocols/reports. The documentation format is illustrated in the VMP. 

A specific, detailed description of the bioanalytical method should be written. This can be in the form of a protocol, study plan, report, and/or standard operating procedure (SOP). All experiments used to make claims or draw conclusions about the validity of the method should be presented in a report (method validation report). 

The management and use of the system, and related reference data (e.g., laboratory reference ranges and coding dictionaries), should be controlled by Standard Operating Procedures. Such procedures should include taking data extracts, possibly as predefined reports. Extracts should be validated to demonstrate they correctly identify, combine/merge, and report data requested. At the system level the functionality of a reporting system should ensure that ... 

The OECD covers a series of activities and personnel. Responsibilities, training, quality assurance (QA), standard operating procedures (SOPs), study plans and study reports, data production and recording, equipment maintenance and calibration, computers and validation, test systems and test substances, and archiving are the primary areas covered by the GLPs. 

The standard operating procedure (SOP) manual contains the procedures validated by the laboratory it is a complete set of instructions for pre-analytical, analytical and post-analytical methodology and also procedures for quality assurance/control, chain-of-custody and security. Each step in the handling of the specimen should be evaluated, optimized where possible and documented in the SOP. Important steps in the analytical process include collection, transport and accessioning of the specimen, sample preparation, isolation and detection of the analytes, production of the report and disposal of the specimen. This chapter focuses on the quality assurance and control issues for analytical method development and validation as well as statistical representation of the data. 

It is counted among the responsibilities of test facility management to ensure that appropriate and technically valid Standard Operating Procedures are. .. followed , even though Study Directors and Quality Assurance personnel would certainly be in a better position to judge the observance of SOPs by study personnel. The real importance of this responsibility lies thus less in the detailed remonstrances with single persons, or admonitions of individual errors, but in the stipulation that management has to act and to implement adequate measures if Quality Assurance reports a less than optimal observance of SOPs. 

Study Audit A comparison of raw data and associated records with the interim or final report in order to determine whether the raw data have been accurately reported, to determine whether testing was carried out in accordance with the study plan and Standard Operating Procedures, to obtain additional information not provided in the report, and to establish whether practices were employed in the development of data that would impair their validity. 

The Validation Team has overall responsibility for validating the facility. The Quality Assurance Manager has responsibility for approval of all validation protocols, final reports, standard operating procedures, chemical and microbiological testing, as well as other critical cGMP documentation. 

The conference report from the Crystal City III Workshop outlines the documentation requirements in detail [10]. The degree of documentation should be sufficient to recreate the validation. Prior to initiating a prestudy validation, an appropriate standard operating procedure or a detailed validation plan should be written. This plan can be a stand-alone document or can be contained in a laboratory notebook or some comparable format. The documentation should clearly state the intended use of the method and a summary of the performance parameters to be validated. The plan should include a summary of the proposed experiments and the target acceptance criteria for each performance parameter evaluated. 

Cross-validation is discussed by Viswanathan et al. [2] in the report from the 2006 Crystal City III AAPS workshop/conference Cross-validation procedures and acceptance criteria need to remain flexible considering the various bioanalytical situations where it would be (may be) required. Specific cross-validation criteria should be established a priori in a standard operating procedure (SOP). ... 

If the bioanaiyticai method is performed according to good laboratory practice (CLP), the method is described in a standard operating procedure (SOP) and the validation method is reported accordingly. In general, validated methods are used in preclinical development for toxicokinetic studies and in clinical development for all studies in which pharmacokinetics is evaluated. 

The validation of data also is an important step in the process. Validation begins at the station with standard operating procedures for self-consistency of operations and maintenance and with systematic calibration of instruments. Air quality instruments are not particularly reliable so that frequent, careful calibration is required for useful data acquisition. Validation of data is continued after transmission before archiving. To maximize reliability, validation involves a dedicated scientist and engineer whose experience permits identification of possible errors or inconsistencies in reported observations. Finally, the validation process is cross-checked with station performance audits and laboratory intercomparisons to identify discrepancies in analytical procedures. This chain of activity generally makes air quality a rather expensive commodity, a fact that is not appreciated by many users. 

The overall project itself requires formally structured planning and control in addition to the validation plans for the computerized operation. To provide this, a project and quality plan from the pharmaceutical manufacturer (or its nominated main contractor) is normally developed as a separate and complimentary document and needs to overview all activities, resources, standards, and procedures required for the project. The plan should define project-execution procedures, quality management procedures, engineering standards, project program, and project organization (with authorities and reporting responsibilities), and reference the project validation plan. There are instances in which the project and quality plan and the project validation plan can be combined into one document. 

For a similar reason, DOE committed to a requirement that safety-related computer codes, which are used in safety analyses affecting the Safety Analysis Report (SAR), Technical Specifications, Technical Standards, Mechanical Standards, Technical Manuals, and Reactor Operation Procedures, be identified, verified, validated, and certified. The personnel who perform safety analyses are also required to be certified. Computer models included in safety analyses are required to conform to Quality Control and Quality Assurance procedures and to be controlled and referred to in new or revised safety analyses. 

The Savannah River Site (SRS) reactor operation has traditionally been controlled by the instructions in detailed operating procedures. In 1975, safety requirements were established in the Technical Specifications and more specific controls were established in the Technical Standards to identify overall plant safety requirements, which were previously determined by supervisors. The supervisor was responsible for understanding and interpreting the technical bases supporting these documents, which were described in other safety documents such as technical reports and technical manuals. It was determined that this process was deficient in human factors considerations, that it lacked an integrated approach, and that the validity of some of the technical bases were not well established and documented. 

During remedial operations, large costs can be incurred if cleanup operations are delayed by slow response in the analysis of samples. Thus, analytical techniques must be available to verify that a cleanup criterion has been achieved and to indicate during cleanup efforts whether to stop or proceed. Preliminary discussions of proposed excavation approaches led to the requirement of 20 to 25 analyses within a 24-hour period. The standard EPA contract laboratory procedure required a minimum of 72 hours elapsed time including data reporting and data validation by EPA. Unfortunately, available protocols such as the EPA Contract Laboratory (CLP) mechanism, typically required two weeks or longer to produce verified data. Alternatives were needed to meet the unique demands of site remediation. 

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