Validated programming

One question of chief interest concerns the number of runs that can be run with one individual SEC column. The lifetime of the sorbent itself must be tested as well as the maximum run number for the packed column. Because column packing procedures for SEC columns are rather time-consuming and all SEC columns have to be checked very carefully with respect to performance, very frequent repacking of the column is unreasonable. Therefore, CIP protocols are generally necessary. The CIP protocol should be developed as part of the process validation program. 

All formulas are to be written out by hand with the specific numbers in the right places on a sheet provided for the purpose, and the calculations are to be done by calculator. Caution Write the numbers exactly as printed, do not round any digits, or the quality assurance unit (a sort of corporate vice squad) will not approve the report out of fear that someone could have cheated. A validated program can be used. While an Excel spreadsheet as such needs no validation, a simple cell-formula calls for extensive tests and documentation and proof that the sheet is password protected against fraudulent manipulation. On top of that, the analyst s supervisor is required to confirm the calculation and sign off on... 

ASSAY2.dat As part of a large validation program, 40 samples were pulled from a production batch. One measurement points to either a gross inhomogeneity or an analytical error the trend of the others could indicate variations in the manufacturing process. 

Full acceptance of HPLC/MS methods by the US EPA OPP as enforcement methods occurred between 1998 and 2001. For example, in 1998, the EPA OPP accepted HPLC/MS (without MS/MS) methods as primary enforcement methods, and high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) only was suitable for confirmatory methods. However, in 2001, HPLC/MS/MS methods also became acceptable for primary enforcement. Table 4 summarizes the types of methods that were validated by the EPA OPP method validation program, for both food tolerance enforcement methods and environmental chemistry methods. 

The Hydrogen Bus Technology Validation Program in Davis/ Sacramento, California is a multi-district partnership of the City of Davis, Yolo County Transportation District (YCTD), University of California, Davis (UC Davis), UniTrans (Transit authority for the City of Davis and UC Davis), and NRG Tech. 

Approaches to Process Validation Process Validation Program Periodic Review of Validated Systems Cleaning Validation Validation of Analytical methods Change Control, Rejection, and Reuse of Materials Rejection Reprocessing Reworking... 

The quality of PW and WFI is constantly monitored. The FDA has provided guidance for the validation of water systems. The validation program consists of three phases. Phases 1 and 2 are for 2-4 weeks each of continuous sampling and testing of water to establish the effectiveness of the pretreatment and purification and distillation processes. Phase 3 is routine monitoring of the water quality over the remainder of a 1 year period to gauge the influences of seasonal conditions on the water quality. 

HPLC is the leading Analytical procedure used for the verification of pharmaceutical cleaning validation programs. HPLC provides a linear, sensitive method for quantitating low levels of residues making the chromatographic finish the most reliable part of the cleaning verification. 

During the last 10 years it has been attempted to develop in vitro methods as alternative methods in the study of effects where animal models have previously been necessary. Such effects include skin and eye irritation and specific organ damage. Validation programs have been launched, and some of the above-mentioned methods have been sufficiently validated for use in regulatory risk assessment of chemical substances and may now for certain purposes be used as stand-alone evidence. Results from nonvahdated methods can in some cases be used as supportive evidence to human and animal data. 

Recent overviews (2), examples (3), and our own experimental efforts (4,5) raised concerns about the reproducibility of a proportion of published data inferring to novel potential targets for a given disease, further highlighting the need for robust target validation programs in the pharmaceutical industry setting. 

Ruggedness testing is one part of an overall method validation program and it is therefore important to begin this chapter by giving a brief outline of the levels of protocols for validation showing clearly where the ruggedness test is performed. 

Figure 5.1 shows the various characteristics and stages in a method validation program. For most quantitative methods of analysis, the method characteristics that require evaluation are accuracy, sensitivity, selectivity, precision and method limitations. Each of these characteristics have contributions from various effects, all of which require consideration within a method validation study. 

Figure 5.1 Representation of a method validation program including the characteristics to test and some of the possible methods for a method...

The study of the precision of a method is often the most time and resource consuming part of a method validation program, particularly for methods that are developed for multiple users. The precision is a measure of the random bias of the method. It has contributions fi om the repeatability of various steps in the analytical method, such as sample preparation and sample injection for HPLC [5-9], and from reproducibility of the whole analytical method fiom analyst to analyst, fiom instrument to instrument and fiom laboratory to laboratory. As a reproducibility study requires a large commitment of time and resources it is reasonable to ensure the overall ruggedness of the method before it is embarked upon. 

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

The purpose of writing fundamentals of validation SOPs is to assist the parent company, affiliates, and contract manufacturers to understand and maintain the validation program to meet the GMP requirements. 

It is the responsibility of the quality assurance manager to develop and maintain the validation program. The departmental managers and contractors are responsible for the SOP compliance. 

The purpose of the validation program was to assure that accurate personal sampling and analytical methods would be available for use by OSHA in monitoring for non-compliance to the OSHA permissible exposure limits (PEL s). The methods are available to others who may want to use them to determine worker exposure to the substances in the OSHA regulations. 

Association of Official Analytical Chemists (AOAC) International (2000), Method validation programs (OMA/PVM Department), including Appendix D Guidelines for collaborative study procedures to validate characteristics of a method of analysis, available http //www.aoac.org/vmeth/devmethno.htm. 

A validation protocol is a document that describes the item to be qualified, the tests and checks to be performed, as well as the results that are expected to be obtained. It is a file in which the records, results, and evaluation of a completed validation program are assembled. It may also contain proposals for the improvement of processes and/or equipment [1]. Validation protocols are important in ensuring that documented evidence is taken which demonstrates that an equipment item, a system, a process, or a method consistently performs at a specified level... 

The physicochemical characteristics of raw materials play an important role in content uniformity and bioavailability. Therefore, bioavailability of the drug over time must be thoroughly investigated before any significant changes are made. Once the physicochemical properties of drug substances (e.g., particle size of raw materials) can influence the availability and clinical effect of a product, the main characteristics of raw materials should be considered in a validation program. The... 

The validation program generally follows the following order ... 

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