Documentation standards validation record

The standard requires validation results to be recorded and design failures to be documented in the validation records. 

Howard Garston-Smith, formerly of Pfizer, has published a book on software quality assurance. It provides a postal audit checklist reproduced in Appendix 7C. If the supplier has already prepared an internal ISO 9000 mapping or an internal audit report on how it aligns to industry standards such as the GAMP Guide, this can be offered as an alternative to the auditor s postal checklist. A reduced postal checklist may be agreed upon, at the very least. Wherever possible, photocopies of actual example documents and test records should be inspected for documentary evidence of validation. Remember that the pharmaceutical and healthcare companies are themselves being inspected for documentary evidence of validation. 

This section contains forms for documenting that all training requirements have been met, sample preparation instructions as necessary to the execution of the validation experiments, and data recording forms. Places for signatru es for performance and review should be included on each form as appropriate to company quality and documentation standards. For examples, see Tables 2 and 3.]... 

The USP methods contained in the monographs are considered validated. The USP states ... users of analytical methods described in USP-NF are not required to validate the accuracy and reliability of these methods but merely verify their suitability for use. Recognizing the legal status of the USP and NF standards, it is essential, therefore, that proposals of new or revised compendial analytical procedures are supported by sufficient laboratory data to document their validity. The Code of Federal Regulations also recognizes that USP methods are validated. The section on laboratory records [8] states Laboratory records shall include completed data derived from all tests necessary to assure compliance with established specifications and standards,... and further states if the method employed is in the current revision of the United States Pharmacopeia [or] National Formulary... and the referenced method is not modified, a statement indicating the method and reference will suffice [8]. 

One final comment The distinction between calibration and validation is a little subtle. In fact, some authors refer to calibration as a subset of validation, and use brute-force validation to mean the noncalibration method of validation. Calibration requires that you (or a subcontractor) show that the source agrees with some higher level standard (within some known and acceptable tolerance) which can be traced to an acceptable (usually national) standard. Brute-force validation shows that use of your process yields an acceptable product. For example, it might be acceptable to use an uncalibrated (but stable) source for in-process tests, performing only the final acceptance test with a traceable calibrated source. In either case, to deliver a satisfactory product and to satisfy auditors you must show that the source works in your processes, and maintain a document (the quality record) showing how that validation was done. 

Equipment used in GLP studies must be validated for appropriateness. Each piece of equipment must have SOPs for operation, calibration, and routine maintenance. All routine and nonroutine maintenance must be documented. What is the definition of a piece of equipment Any item that can have an impact on the results of an anal5dical procedure. In the typical non-GLP laboratory, records are kept on analytical equipment such as spectrophotometers or gas chromatography units. Under GLP, however, the definition expands to include items such as pipets, thermometers, incubators, refrigerators, and mixing devices, as long as it is possible that the use of the item can affect the outcome of the test. For the non-GLP lab, implementation of this standard will dramatically increase the number of equipment-related SOPs. 

The requirements for hardware validation are identical to those of any other equipment in use, comprising the OQ/IQ/PQ cycle, except that in the PQ, it is the test of software used. The software validation comprises functional testing, in which defined inputs produce outputs that meet expectations or specifications a thorough examination of source codes, database designs, programming standards, control methods, and support documentation or a quality-assurance program that includes alternate plans, contingency practices, record retrieval, and security practices... 

Conventional method development records are typically not the subjects of regulatory review. Failures, which are commonplace in early method development, are rarely investigated or fully explained. Laboratories that plan to use development data in a validation must document their data in accordance with regulatory standards. Therefore, all entries must be recorded in laboratory notebooks that shall be readily available for authorized inspection [6]. 

Standard operationg procedures (SOPs) incomplete, not current, or not available to the operators in the production area Batch production records incomplete, not recorded at time of operation, or not specific enough to document significant process steps Cleaning procedures not validated or not including all processing equipment and transfer implements (scoops, etc.)... 

Validation test environment including hardware, software System security including passwords, network rights, functional security, physical security, modem access and virus protection Validation test environment including related documents, along with standard operating procedures, user manuals, and system development/ maintenance and documentation Validation assumptions, exclusions, and limitations Responsibilities matrix Validation data sets Acceptance criteria Expected results Execution of the validation plan Resolution of errors Documentation Training records... 

Add a section for comments, as well as a place for signatures for the personnel who reviewed the training records and conducted the validation training in accordance with company quahty standards for training documentation. 

As part of a laboratory s quality control program, all steps of the test should be described separately, and parameters of each step established and monitored in order to ensure consistency of performance and reproducibility of results. Daily records of control results are maintained, and corrective actions are undertaken and documented when results are unacceptable. In practice the surgical pathology histology laboratory typically falls short of the ideal standards in key areas, especially with regard to tissue preparation. In this section, we will discuss quality control issues as they pertain to the validation of antibodies and the use of controls. We will also address measures that may be adopted to minimize variability deriving from inconsistent tissue preparation, including fixation. 

Reagents and reference materials Likely will change but should have some documentation on early characterization Continue to screen for optimal reagents Lot no. and history (notebook reference) Evaluate different reagents and identify critical reagents Determine if sufficient quantities are available and their stability for later bioanalytical needs Include C of A for reference materials in assay validation documents Keep records of source and lot no. Use optimized capture/ detection reagents Use characterized reference standard from final manufacturing process with Cof A Record all lot nos. and sources... 

At a minimum, documentation of the characterization and stability of a standard, such as a certificate of analysis (Co A) and/or a certificate of stability (CoS), is typically available from the suppliers. The certificate should be obtained and recorded. The quantity of reference standard is typically limited in commercial kits designed for research use, and it is not uncommon that the reference material values may differ substantially between lots and manufacturers [16]. Novel biomarkers rarely have established gold standards against which their potency and abundance can be calibrated. A comparison of available sources can be useful, and when validating an assay for advanced applications it is desirable to plan ahead to obtain and reserve a sufficient supply of the same reference material. The example in Fig. 6.5 compares three reference standard curves, each prepared from a concentrated stock solution from a commercial supplier, an in-house reference standard, and a commercial kit, respectively. The instrument responses (optical density, OD) were highest with the standard from the commercial stock, the lowest with the kit, while the in-house reference standard response was intermediate. In this case, either the same commercial stock or the in-house reference standard can be used throughout the clinical study. 

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